The present invention pertains to compositions of random or columnar hydrogel colloidal crystals in water-organic solvent mixture and methods of making such crystals. More specifically, the compositions of hydrogel colloidal crystals are made from mixing an aqueous suspension of poly-N-isopropylacrylamide (“PNIPAM”)-co-allylamine microgels with dichloromethane, forming a PNIPAM-co-allylamine/dichloromethane mixture. The PNIPAM-co-allylamine/dichloromethane mixture is incubated for a period of time at a given temperature, forming the colloidal crystal material. The colloidal crystals can be stabilized by diffusing a glutaric dialdehyde solution into the colloidal crystal material. The concentration of polymer matrix microgels can determine the orientation of random or columnar crystals.
Hydrogels. Gels are three-dimensional macromolecular networks that contain a large fraction of solvent within their structure and do not dissolve. When the trapped solvent is water, the gels are termed “hydrogels.” Hydrogels exhibit high water content and are soft and pliable. A hydrogel can be also defined as a colloidal gel in which water is the dispersion medium of the colloid having a mixture with properties between those of a solution and fine suspension. A colloid gel is a colloid in a more solid form than a sol. The properties of hydrogels are similar to natural tissue, and therefore hydrogels are extremely biocompatible and are particularly useful in biomedical and pharmaceutical applications. As such, hydrogels can be responsive to a variety of external, environmental conditions. A unique physical property of some hydrogel systems is reversible volume changes with varying pH and temperature.
Generally, polymer gels can be formed by the free radical polymerization of monomers in the presence of a reactive crosslinking agent and a solvent. They can be made either in bulk or in nano- or micro-particle form. The bulk gels are easy to handle, but usually have very slow swelling rates and amorphous structures arising from randomly crosslinked polymer chains. In contrast, gel nanoparticles react quickly to an external stimulus, have organized local structure, but suffer from practical size limitations.
Responsive polymer gels can be made by the co-polymerization of two different monomers, by producing interpenetrating polymer networks or by creating networks with microporous structures. These processes are disclosed in U.S. Pat. Nos. 4,732,930, 5,403,893, and 6,030,442, respectively. Finally, a microparticle composition and its method of use in drug delivery and diagnostic applications have also been disclosed in U.S. Pat. No. 5,654,006.
Hydrogels usually consist of randomly crosslinked polymer chains and contain a large amount of water occupying interstitial spaces of the network, resulting in amorphous structures. Without the addition of a coloring agent or opacifier, hydrogels are clear and colorless when they are fully swollen in water. To create colors in hydrogel systems, there are two major approaches in the prior art as disclosed in U.S. Pat. Nos. 6,165,389, 6,014,246 and 6,187,599. The first is to form a poly(N-isopropylacrylamide) (P-NIPA) crystalline colloidal fluid in an aqueous media and contain it in a glass cell. The second is to embed a crystalline colloidal array of polystyrene polymer solid spheres in a P-NIPA hydrogel. Both approaches have utilized the unique temperature-responsive property of the P-NIPA, but each has its own limitations. The first material is a colloidal fluid: its crystal structure can be easily destroyed by a small mechanical vibration. The second approach to make colored hydrogels requires the introduction of non-hydrogel solid spheres (polystyrene) as light-diffracting materials.
Crystal Hydrogels. The concept for synthesizing crystal hydrogels based on crosslinking gel nanoparticles was previously described in U.S. patent application Ser. No. 10/295,484 filed by Hu et al., on Nov. 15, 2001 and titled “Synthesis, Uses and Compositions of Crystal Hydrogels,” (“the '484 Application”). The '484 Application described nanoparticle networks that exhibit either a uniform color due to a short-range ordered structure or are colorless due to a randomly ordered structure. Additionally, the '484 Application discloses a method for creating hydrogels with ordered crystalline structures that exhibit a characteristic colored opalescence. In addition to the unique optical properties, these materials contain a large amount of water in their crosslinked networks. The manufacturing processes include synthesizing monodispersed hydrogel nanoparticles containing specific reactive functional groups, self-assembly of these particles to form a crystalline structure, and subsequent crosslinking neighboring spheres to stabilize the entire network. Polymerizing a hydrogel monomeric composition around the crystalline structure can enhance the mechanical strength. The resulting network is dimensionally and thermodynamically stabile under various pH and temperature conditions. The color and volume of these crystalline hydrogel networks can reversibly change in response to external stimuli such as temperature, pH and other environmental conditions. The primary scope of this invention relates to environmentally responsive hydrogel nanoparticle networks that exhibit crystalline structures, are opalescent in appearance, are stable under mechanical vibration and temperature fluctuations, and consist of only hydrogel materials without other embedded solid polymer spheres. These new materials may lead to a variety of technological and artistic applications, ranging from sensors, displays, controlled drug delivery devices, jewelry and decorative consumer products. The '484 Application is specifically incorporated herein by reference.
Columnar Hydrogel Colloidal Crystals. Useful methods of obtaining colloidal crystals have been previously developed and include: sedimentation,[1-3] diffusion of base,[4] evaporation,[5] electrostatic repulsion,[6] templated growth,[7] gradient temperature fields,[8]and physical confinements [9] is of paramount importance. Such crystals allow one to obtain useful functionalities not only from colloidal particles but also from the long-range ordering of these particles.[10-12] A useful method of growing large columnar crystals by mixing an aqueous suspension of hydrogel colloids (or microgels) with organic solvent is described herein. The hydrogel colloidal crystals of several centimeters have grown from the top to the bottom along the gravity direction, driven by coalescence of micelles consisting of organic oil droplets coated by many microgels. This is in contrast to a conventional method to form randomly-oriented hydrogel colloidal crystals in pure water with the largest domain size of the order of several minimeters.[13-16]
Columnar crystals of hard spheres have been studied using a sedimentation [3] or a diffuse of base method.[4]In these experiments, the silica spheres were dispersed in an aqueous solution at volume fractions less than the freezing value [3] or in an pH gradient solution [4] to settle down on a flat surface to form columnar crystals. These methods and other previous ones cannot be used for hydrogel colloids. This is because in contrast to silica or polystyrene hard spheres, the hydrogel colloids or microgels investigated in this work contain 97 wt % water. Consequently, the density and the hydrogel colloids refractive index of the microgels closely match up those of the surrounding water, yielding a condition of mini-gravity (˜10−2g) at room temperature.[16]0 It is difficult, if not impossible, to grow columnar crystals by natural sedimentation of microgels in water. Currently, the major method for preparing hydrogel colloidal crystals has relied on self-assembling hydrogel particles in water, forming randomly oriented crystal domains.[12-16] Hydrogels are well known for their unique hydrophilic and environmentally responsive properties that lead to various applications including controlled drug delivery, artificial muscles, devices and sensors.[17-24] Assembling hydrogel colloids along a single direction could open a new avenue for these applications.
Conventional hydrogels are isotropic materials. That is, their swelling ratio, optical transmission, and molecular diffusion properties are the same along different directions. The isotropic symmetry may be broken only under an external constrain such as stretching or by incorporating liquid crystals into gels. The hydrogel with a columnar crystal structure, as described herein, can behave differently along the crystal growth axis and along the direction that is perpendicular to the growth axis. For example, it is found that the gel swells more along the direction that is perpendicular to the long axis of the columnar crystals than along the direction of the long axis. Some proteins may diffuse fast along the columnar crystals.
Uses of Responsive Gels. Some diversified uses of responsive gels include solute/solvent separations, biomedical tissue applications, devices, and in NMR contrast agents. For example:
U.S. Pat. No. 5,532,006 issued to Lauterbur, et al., on Jul. 2, 1996, titled “Magnetic Gels Which Change Volume in Response to Voltage Changes for MRI,” (“the '006 Patent”) is specifically incorporated herein by reference. The '006 Patent disclosed compositions that are useful in nuclear magnetic resonance imaging comprising a matrix which exhibits a volume phase change in response to an electric field, the matrix containing a magnetic and preferably superparamagnetic component distributed therethrough.
U.S. Pat. No. 5,976,648 issued to Li, et al., on Nov. 2, 1999, titled “Synthesis and Use of Heterogeneous Polymer Gels” (“the '648 Patent”) is specifically incorporated herein by reference. The '648 Patent disclosed a heterogeneous polymer gel comprising at least two gel networks. One embodiment of the present invention concerns a heterogeneous polymer gel comprising a first gel network comprising an environmentally-stable gel and a second gel network comprising an environmentally-unstable gel wherein the first gel network interpenetrates the second gel network. The heterogeneous polymer gel exhibits controlled changes in volume in response to environmental changes in condition, such as of temperature or of chemical composition.
U.S. Pat. No. 5,062,841 issued to Siegel on Nov. 5, 1991, titled “Implantable, Self-Regulating Mechanochemical Insulin Pump,” (“the '841 Patent”) is specifically incorporated herein by reference. The '841 Patent disclosed an implantable pump for the delivery of insulin to a mammal has a biocompatible housing which supports an aqueous-swellable glucose-sensitive member and a chamber containing a pharmaceutically acceptable insulin composition. The aqueous-swellable member is exposed to the body fluids which surround the pump when it is implanted; it initiates an insulin pumping cycle by swelling in response to an increase in blood glucose level and terminates an insulin pumping cycle by deswelling in response to the decrease in blood glucose level. When the glucose-sensitive aqueous-swellable member swells in response to an increase in blood glucose level, it generates a hydraulic force which causes insulin composition to be expelled from the chamber through a pressure-sensitive one way valve. The valve seals the chamber when the hydraulic force is withdrawn by deswelling of the glucose-sensitive aqueous-swellable member.
U.S. Pat. No. 4,912,032 issued to Hoffman, et al., on Mar. 27, 1990, titled “Methods for Selectively Reacting Ligands Immobilized Within a Temperature-Sensitive Polymer Gel,” (“the '032 Patent”) is specifically incorporated herein by reference. The '032 Patent discloses methods for delivering substances into, removing substances from, or reacting substances with a selected environment utilizing polymer gels or coatings characterized by a critical solution temperature (CST) are disclosed. The CST as well as the pore structure, pore size, pore distribution, and absorbing capacity of the gel may be selectively controlled. The substances may be physically or chemically immobilized within the polymer gels. In addition, a method for altering the surface wettability of CST polymers is also disclosed.
U.S. Pat. No. 4,555,344 issued to Cussler on Nov. 26, 1985, and titled “Method of Size-Selective Extraction from Solutions,” (“the '344 Patent”) is specifically incorporated herein by reference. The '344 Patent disclosed a separation method utilizing the ability of cross-linked ionic polymer gels to selectively extract solvent from a solution of a macromolecular material. A feed solution containing macromolecules is added to a small amount of basic or warm gel. The gel swells, absorbing the low molecular weight solvent, but cannot absorb the large macromolecules. The raffinate, which is now a concentrated macromolecular solution, is drawn off. To regenerate, a little acid is added to the filtered gel, or the gel is cooled, so its volume decreases sharply. The solvent is expelled from the shrinking gel and is then drawn off, leaving only the collapsed gel. A base is added to the gel, or the gel is warmed. More feed solution is added, and the cycle is begun again.
The primary scope of the present invention relates to the compositions and production methods for columnar hydrogel colloidal crystals in a water-organic solvent mixture.